This invention relates to the fields of chemistry, bacteriology, biology, biochemistry, pharmacology and medicine. In particular it relates to two new antibiotics isolated from a fermentation broth of a novel strain of Microbispora corallina. 
Over the past 60 years, a broad range of antibiotics, have become available for the treatment and prevention of bacterially transmitted disease. Penicillin, streptomycin, aureomycin, cephalosporin, bacitracin, erythromycin, novobiocin, methicillin, neomycin, chloramphenicol, kanamycin, chlortetracycline,to name a fewxe2x80x94each of these drugs, isolated from microorganisms, has provided a great benefit to the well-being of people and animals the world around. Unfortunately, the widespread use of antibiotics, combined with the natural proclivity of target organisms to find a way to survive such attack, has resulted in an alarming increase in the number of resistant bacterial strains. This roster of resistant species includes a number of clinically important bacteria such as Staphylococcus, Salmonella, Enterobacteriaceae and Pseudomonas, in particular, the species S. aureus and S. pneumoniae. Thus, there continues to be an urgent need for new drugs, exhibiting novel modes of action unrecognized by target organisms, to overcome the resistance of these and other species of bacteria.
While a great deal of effort is being expended to design new, partially or entirely synthetic drugs to fill the voids in therapeutic efficacy created by the emergence of resistance, nature continues to be a invaluable source of such compounds.
Thus, the present invention relates to two antibiotics designated MF-BA-1768xcex11 and MF-BA-1768xcex21, to their production by fermentation, to methods for their recovery and concentration from fermentation broth, and to processes for their purification. It includes within its scope the antibiotics in dilute form, in crude concentrates, in complexes of various or all components, and in pure form as individual compounds. The present invention also includes a novel strain of Microbispora corallina, which produces the compounds. The strain is identified by the DNA sequence that codes for its partial 16S rRNA sequence and by its nutrient utilization pattern. The chemical structures of the new antibiotics are presently unknown but four potential structural features have been deduced based on partial 2-D NMR data including 1Hxe2x80x941H correlation (COSY) and 1Hxe2x80x9413C correlation (HMQC). The compounds are characterized by their physical and chemical properties including UV, IR, and 1H NMR spectra. Their molecular weights were determined by ESI-FTMS.
In one aspect, this invention relates to antibiotic MF-BA-1768xcex11, or a pharmaceutically acceptable salt thereof, having the physicochemical characteristics, in the non-salt form, described in detail below.
In another aspect, this invention relates to antibiotic MF-BA-1768xcex21, or a pharmaceutically acceptable salt thereof, having the physicochemical characteristics, in the non-salt form, described in detail below.
In a further aspect, this invention relates to a process for producing antibiotic MF-BA-1768xcex11, comprising cultivating a strain of Microbispora corallina, NRRL 30420, or an antibiotic MF-BA-1768xcex11-producing mutant, variant or recombinant form thereof, in a culture medium containing assimilable sources of carbon, nitrogen and inorganic salts under aerobic fermentation conditions until antibiotic MF-BA-1768xcex11, is produced and then recovering the antibiotic therefrom.
In a still further aspect, this invention relates to a process for producing antibiotic MF-BA-1768xcex21, comprising cultivating a strain of Microbispora corallina, NRRL 30420, or an antibiotic MF-BA-1768xcex21-producing mutant, variant or recombinant form thereof, in a culture medium containing assimilable sources of carbon, nitrogen and inorganic salts under aerobic fermentation conditions until antibiotic MF-BA-1768xcex21, is produced and then recovering the antibiotic therefrom.
An aspect of this invention is a biologically pure culture of Microbispora corallina, NRRL 30420, or an antibiotic MF-BA-1768xcex11-producing mutant, variant or recombinant form thereof.
An aspect of this invention is a biologically pure culture of Microbispora corallina, NRRL 30420, or an antibiotic MF-BA-1768xcex21-producing mutant, variant or recombinant form thereof.
A bacterial strain comprising DNA SEQ. No. 1, or a sequence having at least 80% homology therewith, is an aspect of this invention.
An aspect of this invention is a pharmaceutical composition comprising a therapeutically effective amount of compound MF-BA-1768xcex11 and a pharmaceutically acceptable carrier, wherein compound MF-BA-1768xcex11 has the physicochemical characteristics described in detail below.
An aspect of this invention is a pharmaceutical composition comprising a therapeutically effective amount of compound MF-BA-1768xcex21 and a pharmaceutically acceptable carrier, wherein compound MF-BA-1768xcex21 has the physicochemical characteristics described in detail below.
An aspect of this invention is a method for treating a bacterial infection comprising administering to a patient in need thereof a therapeutically effective amount of compound MF-BA-1768xcex21, which has the physicochemical characteristics described in detail below.
An aspect of this invention is a method for treating a bacterial infection comprising administering to a patient in need thereof a therapeutically effective amount of compound MF-BA-1768xcex21, which has the physicochemical characteristics described in detail below.
A further aspect of this invention is either of the preceding two methods wherein the infection-causing bacteria are from the genera Staphylococcus, Enterococcus, Streptococcus, Haemophilus or Escherichia.
An aspect of this invention is the above methods wherein the infection-causing bacteria are Staphylococcus aureus, Staphylococcus epidermis, Staphlyococcus haemolyticus, Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae, Streptococcus pyrogenes, Haemophilus influenzae or Eschericia coli. 
Table 1 is a list of the cultural characteristics of Microbispora corallina strains MF-BA-1768, JCM 12066, and JCM 12067.
Table 2 is a carbon source utilization listing for Microbispora corallina strains MF-BA-1768, JCM 12066, and JCM 12067